Gel wound dressing

ABSTRACT

This invention relates to a gel wound dressing material, and to techniques for preparing and using such a material. The invention provides a gel wound dressing in which the polymer component comprises a copolymer of a starch and a monounsaturated carboxylic acid or an ester or salt thereof, the copolymer being in the form of particles of which at least 70% by weight have a size of not more than about 100 um; and water. 1.

This application is a 35 USC 371 of PCT GB95/01804 filed Jul. 31, 1995.

This invention relates to a gel wound dressing material, and totechniques for preparing and using such a material.

It is desirable to control the condition of a wound to encourage thehealing process by maintaining it sufficiently moist so as to absorb orto eliminate the formation of dry crusty tissue in the vicinity of thewound, while also absorbing materials exuded from the wound, includingdead leucocytes, epidermal and dermal cells. At the same time, it isdesirable to prevent access to the wound of agents, whether bacterial orfungal, which can lead to infection. Examples of wounds to which thesefactors are relevant are ulcers, traumatic and surgical wounds, andburns, and tissue donor sites.

Traditionally, wounds have been encouraged to heal by placing a gauzematerial over the wound. More recently, however, it has been proposed toapply a gel material over the wound. A suitable gel material isdisclosed in U.S. Pat. No. 4,226,232. It comprises a hydrolysedcopolymer of starch-and an acrylonitrile. The polymer is prepared in gelform by mixture with water, to an extent which gives the copolymer anappropriate viscosity which enables it to be manipulated as a gel,especially when applying it to a wound and while it is applied to thewound. Modified such materials are disclosed in U.S. Pat. No. 4,302,369,in which the polymer is converted to its aluminium salt to increase itsability to absorb solutions with a high ionic strength.

Appropriate properties for a gel, for use as a wound dressing include aviscosity that makes the material capable of being manipulated beforeadministration to a wound and then applied appropriately over the areaof the wound, and an ability to absorb exudate from the wound. The needto be able to manipulate a gel material for a wound dressingconveniently has to be balanced with the ability of the gel to absorbadditional liquid; the mixture of the polymer with water to confer thegel viscosity on the polymer will result in a reduction of the abilityof the polymer to absorb liquid.

The present invention provides a gel-wound dressing in which the polymercomponent comprises a copolymer of a starch and a monounsaturatedcarboxylic acid or an ester or salt thereof.

Accordingly, in one aspect, the invention provides a gel wound dressingwhich comprises:

(a) a water absorbent copolymer of a starch and a mono-unsaturatedcarboxylic acid or an ester or salt thereof; and

(b) water.

The dressing material may further comprise a preservative or otheradditive.

The dressing of the invention has the advantage that it can be providedas a gel, and therefore be manipulated conveniently before applicationto a wound and while it is so applied, with an ability to absorb fluidswhich can be at least comparable with gel wound dressings based on otherpolymer systems. The dressing can also provide appropriate moisturelevels to minimise the risk of a wound drying out during the healingprocess, which can itself give rise to complications in the healingprocess in terms of the formation of crusty tissue. The dressingmaterial of the invention can be made with a viscosity which is at leastabout 100 kcps, preferably at least about 125 kcps, for example at leastabout 160 kcps. The viscosity can be arranged to be not more than about300 kcps, more preferably not more than about 275 kcps, for example notmore than about 250 kcps. The viscosity of the dressing material ismeasured on a Brookfield RVF viscometer with a helipath stand, using aT-bar D spindle at 4 rpm.

The viscosities referred to above can be attained according to thepresent invention while maintaining a high ability to absorb exudedmaterials from the wound as can be demonstrated by means of a salineabsorption test. That test comprises dispersing 2 g of the dressingmaterial in 20 ml of 0.9% aqueous NaCl solution. The dispersion isdecanted into a 50 ml measuring cylinder. Once the dispersion hassettled, the position of the phase separation is noted from which thefluid absorption capacity can be calculated. It has been found that thedressing material of the invention can be made with a viscosity withinthe limits mentioned above, with a saline absorption of at least about200 ml of the solution per 100 g of the wound dressing, preferably atleast about 250 ml.100 g⁻¹, more preferably at least about 300 ml.100g⁻¹. The absorption characteristics of the dressing material have beenfound to be enhanced as a result of a sterilisation step in itspreparation which involves exposing the material to heat and pressure.The viscosity that can be obtained in the material of the wound dressingmaterial of the invention means that the material is capable of beingmanipulated conveniently over the area of the wound that is to betreated using the material. It also facilitates removal of the materialfrom its packaging. In addition to facilitating manipulation, arelatively low viscosity can enable the tackiness of the material to bemaintained relatively low, which reduces damage to the wound when thedressing is removed.

Control of the viscosity is one means of measurement which may be usedto obtain a required ratio between copolymer and water in the gelmixture. However, other means may be adopted, to achieve desiredwater-absorption properties of the gel mixture, which effectivelycomprises required provision of a suitable "spreadable gel". This canrange between "highly mobile" at one extreme to "very stiff" at theother extreme, and which can be obtained by variation of the proportionby weight of copolymer in the gel mixture between about 0.2% to about6%. The particular weight proportion which may be selected can depend onthe particular means adopted to dispense the gel mixture, with e.g. ahighly mobile gel being suitable for introduction into a deep wound by asyringe, and a stiffer gel being suitable for extrusion e.g. from asqueezable sachet so as to be readily spread over the wound area.

In one preferred arrangement, the gel mixture may be stored in asqueezable sachet, and therefore the required properties of the gelmixture will be such that it can be readily be squeezed from the sachet,and to be readily spread over the wound area.

The gel wound dressing of the invention has been found to be capable ofproviding suitable absorption characteristics, in particular towardssolutions which are high in ionic strength, without any need to includealuminium ions. This can represent a significant advantage, inparticular in situations in which the presence of aluminium ions cangive rise to clinical complications.

Preferably, the gel wound dressing is formed from a mixture of particlesof the copolymer and water, in which the distribution of particles issuch that at least about 70% by weight, more preferably at least about80%, especially at least about 90%, have a particle size of not morethan about 100 μm. Preferably, the gel wound dressing is formed from amixture of particles of the copolymer and water, in which thedistribution of particles is such that at least about 60% by weight,more preferably at least about 70%, especially at least about 85%, havea particle size of not more than about 75 μm. Preferably, thedistribution of particles is such that not more than about 10% byweight, more preferably not more than about 6%, have a particle sizegreater than about 100 μm. The particle size distribution can bedetermined using sieves with known mesh sizes, as is known.

It has been found that the use of particles of the copolymer whose sizesatisfies some or all of these conditions gives rise to materials withviscosities which make the copolymer suitable for use in the treatmentof wounds, with the characteristics of a gel. The use of particles ofthe polymer with a size within these ranges has the advantage of makingthe material smoother without a granular texture. The smooth texturemakes the material easier to spread appropriately over a wound that isto be treated. Also the gel usually will be clear i.e. transparent, sothat the wound can be observed while the dressing is being applied.

Preferably, the gel wound dressing of the invention includes a componentwhich reduces its tendency to dry out. This component may also act as apreservative. Examples of suitable materials include polyols, such aspropane-1,2-diol and glycerol, or a mixture thereof. Preferably, thepolyol component is present in the composition in an amount of at leastabout 100% by weight based on the weight of the copolymer, morepreferably at least about 200%, especially at least about 300%, forexample about 400%, and with advantage even up to 600%.

Preferably, the gel wound dressing of the invention includes at leastone other active component. For example, the dressing might include anagent which inhibits or at least reduces the tendency for bacteria tocolonise on the dressing. An example of a suitable such agent is apolyol such as propane-1,2-diol.

Examples of other active components that might be included in thedressing include anaesthetic agents, hormonal compounds and lubricants,enzyme-containing compositions, antibiotics (such as metronidazole),collagen materials, cytokines (such as platelet derived growth factor,insulin-dependent growth factor, and transforming factored placentilegrowth factor), and elastin (preferably with fibrin and fibrinogen).

The copolymer used in the dressing is produced by reaction of a starchwith a monoethylenically unsaturated carboxylic acid, or an ester orsalt of such an acid. Examples of suitable components for the copolymer,together with the starch, include acrylic acid, methacrylic acid, lowercarboxyl (C₁ to C₄) esters thereof and salts such as with elements ofGroups I and II or ammonia. It is preferred that substantially all ofthe carboxyl groups in the copolymer are present as acid groups, or assalt or ester derivatives of acid groups.

A particularly preferred copolymer comprises at least about 50%,preferably at least about 70%, more preferably at least about 85%, forexample at least about 95%, of a salt of a starch grafted polyacrylate.Preferred salts include toe sodium salt.

The copolymerisation reaction between the starch and the acrylatecomponent can be initiated by means of irradiation, for example using anelectron beam, γ-radiation such as from a Co⁶⁰ source, or ultravioletradiation. The reaction can also be initiated by means of a chemicalinitiator such as benzoyl peroxide, hydrogen peroxide or a salt such asa ceric salt.

Examples of suitable copolymers for use in the gel wound dressing of theinvention are disclosed in GB-1512325. Subject matter disclosed in thatdocument is incorporated in the specification of this application bythis reference. The document discloses a water absorbing resin whichcomprises a copolymer of starch and a water soluble monomer such asacrylic acid or a derivative thereof. The resin is crosslinked as aresult of a reaction with a crosslinking agent such as polyesters ofunsaturated mono- or polycarboxylic acids with polyols (for example anester of di-methacrylic acid with ethylene glycol). The resin is said tobe suitable for absorbing fluids such as blood and urine, for example indiapers, sanitary towels and disposable dustcloths for kitchens. Thedisclosed resin can be applied in the form of a powder, in an aqueousdispersion, or by immersion of a substrate in a solution of the resin.The resin is said to be particularly suitable for use in diapers andsanitary towels.

The copolymer used in the dressing of the invention will generally becrosslinked, so as to confer appropriate gel-like properties andviscosity on the dressing material. The crosslinks will preferably beinternal crosslinks. It has been found that the use of a polymer whichis crosslinked in this way gives rise to a smoother dressing material,which has advantages in use for example in terms of its ability to bespread.

The starch used to form the copolymer may be a natural starch such aspotato starch, rice starch, tapioca starch or corn starch, or a modifiedor processed starch such as α-starch, dextrine and oxidised starch.Natural starches are particularly preferred.

The ratio by weight of the starch to the acid derivative component ofthe copolymer is preferably at least about 1, more preferably at leastabout 2, especially at least about 5, for example at least about 10. Theratio is preferably not more than about 10⁴, more preferably not morethan about 10³, especially not more than about 100.

Suitable starch acrylate copolymers for use in the wound dressing of theinvention are available from Hoechst Celanese under the trade markSANWET COS-915.

Preferably, the water that is present in the wound dressing gel is notmore than about 60% of the total water absorbency of the copolymer, morepreferably not more than about 5%, for example not more than about 3%.

The water absorbency of the copolymer is determined by immersing indeionised water a known weight of the gel (1 to 2 g) made to theexemplified formulation, contained in a sealed bag of a hydrophilicpolypropylene based non-woven fabric available from Scimat Limited underthe trade mark SCIMAT 700/13, and recording its weight change after 24hours.

Prior to weighing, the surface of the bag is blotted to remove excesswater and an empty bag is used as a control.

The total absorbency of the resin, measured in ml.g⁻¹, is calculated asfollows: ##EQU1## However, the total water absorbency (T) can bedifficult to measure in practice (due to variation between differentbatches of material), but tests carried out to date give the followingdesired parameters, wherein carrying out measurements for values from900 to 1300 ml/g for pure water: ##EQU2## in which R is the percentageproportion by weight of water present in the gel mixture relative to thetotal water absorbency of the copolymer in the gel mixture; T is thetotal water absorbency; x is the percentage by weight of copolymer inthe copolymer/water gel mixture, and Y=amount of water added in themixing stage.

For values of x=0.2 and T=900 and 1300 and Y=99.8, the values of R werefound to be 55.4 and 38.4 respectively.

For value of x=6, and values of T=900 and T=1300 and Y=94, the values ofR were found to be 1.74 and 1.21 respectively.

The value of x=0.2 gives a gel mixture which is very runny, or "highlymobile" as indicated earlier, whereas the value x=6.0 gives a gelmixture which is very stiff. These two values of x determine the rangewithin which a suitable spreadable gel can be derived, to suitparticular requirements. Therefore, suitable variation of the weightproportions of copolymer and water in the gel mixture may be selected,by experiment, within the range, to provide spreadable gel mixturessuitable for different requirements.

In a preferred example, which contains 3.5 parts copolymer and 75.5parts water, then when T=900, R=2.4; and when T=1300, R=1.66, andY=75.5.

Accordingly, in a particularly preferred range of proportion by weightof copolymer to water in a gel mixture of a gel wound dressing accordingto the invention, the relative proportion of water that is present in aparticular sample, compared with the total water absorbency of thecopolymer in the sample, lies in a range having a minimum value of up to1.0%. The upper limit to the preferred range will be determined byexperiment, but may go up to as high a value as R=60%.

If desired, for certain circumstances it may be advantageous tointroduce substantial amounts of preservative e.g. a polyol into the gelmixture, (which replaces the amount of water required in the formulationof the gel), and this can then result in a lower value of R. By way ofexample, in a gel mixture of 3% polymer, 69% polyol, and 28% water, thevalue of R is reduced to 0.7. The invention therefore includes thepossibility of including weight proportions in the gel mixture ofpolymer, preservative, and water such that R can be less than 1.0%, anddown to at least 0.7%.

The gel dressing will generally be applied to a wound in a layer ofthickness at least about 2 mm, preferably at least about 4 mm, forexample at least about 5 mm. A dressing applied to certain wounds withthis thickness can be left in situ for as much as seven days or more.

The dressing of the invention can be administered in a sachet from whichit can be extruded through an opening, formed for example by means of aknife, by the application of pressure to the sachet.

The dressing can conveniently be administered in a syringe, from whichit can be extruded in a controlled manner directly onto a wound so thatit is appropriately located to ensure that the wetness of the wound iscontrolled.

The dressing can be administered in a porous container such as a pouchor sachet made of a material that is suitably porous to the fluids to beabsorbed by the dressing when in place on the wound. Examples ofmaterials that might be suitable for the sachet or pouch include paperbased materials and organic materials such as polyamides and polyesters,especially in the form of a non-woven sheet.

The wound dressing of the invention can conveniently be applied directlyto a wound. It is envisaged that, in most circumstances, the dressingwill be changed after a period of, perhaps, hours or days, according tothe condition of the wound, for example about 2 to 3 days (althoughshorter periods can be appropriate under certain conditions, for examplewhen the amount of material exuding from the wound is high). When thedressing is to be changed, the gel-like characteristics of the dressingmaterial facilitate its removal from the wound, and which may beassisted by irrigation, for example using a sterile saline solution.

It will generally be appropriate for a secondary dressing to be appliedover the gel wound dressing, to retain it in place on a wound and toprovide a degree of physical protection for the gel dressing. The natureof the secondary dressing will depend on the characteristics of thewound. For example, if the wound has eschar (dry crusty tissue)associated with it, a moisture vapour permeable dressing will beappropriate. If the wound is malodorous, an activated carbon dressingcan be appropriate.

An appropriate secondary dressing can preferably exclude bacteria fromthe wound, retain the dressing material in place on the wound, andpermit exchange of moisture with the atmosphere. Preferably, thedressing is transparent so that the wound can be inspected. Suitablesecondary dressings are sold under the trade marks OPSITE and TEGADERM.

The invention also provides a method of making a gel wound dressingmaterial, which comprises mixing a water absorbent copolymer of a starchand a monounsaturated carboxylic acid or an ester or salt thereof with aquantity of water, the proportions of the copolymer and water being suchthat the resulting mixture has gel properties.

Preferably, the method includes the step of sterilising the gel wounddressing, for example by means of a heating step, optionally underpressure, or by irradiation if the materials of the dressing are notaffected adversely by irradiation. Unexpectedly the saline absorbencycapacity of the sterilised gel is greater than that beforesterilisation.

The invention further provides a method of treating a wound whichincludes the step of applying a gel wound dressing of the type discussedabove.

An example of a gel wound dressing will now be described. The dressingwas made from a starch acrylate copolymer sold under the trade markSANWET COS-915. It is supplied by Hoechst Celanese. Typically it has aparticle size distribution as follows:

We claim:
 1. A gel wound dressing which comprises a mixture of:(a) awater absorbent copolymer of a starch and a mono-unsaturated carboxylicacid or an ester or salt thereof, the copolymer being in the form ofparticles of which at least about 70% by weight have a size of not morethan about 100 μm; and (b) water.
 2. A wound dressing as claimed inclaim 1, which includes a component which reduces the tendency of thedressing to dry out when exposed to atmosphere.
 3. A wound dressing asclaimed in claim 2, in which the said component is a polyol.
 4. A wounddressing as claimed in claim 3, in which the said component comprisespropane-1,2-diol.
 5. A wound dressing as claimed in claim 2, in whichthe said component is present in an amount of at least 100% based on theweight of the copolymer.
 6. A wound dressing as claimed in claim 1,which includes an agent which inhibits or at least reduces the tendencyfor bacteria to colonise on the dressing.
 7. A wound dressing as claimedin claim 1, in which the distribution of the particles of the copolymeris such that at least about 80% have a particle size of not more thanabout 100 μm.
 8. A wound dressing as claimed in claim 1 in whichsubstantially all of the carboxyl groups in the copolymer are present asacid groups, or as salt or ester derivatives of acid groups.
 9. A wounddressing as claimed in claim 1, in which the wound dressing comprises aspreadable gel mixture.
 10. A wound dressing as claimed in claim 1, inwhich the proportion by weight of copolymer lies in the range from 0.2to 6%.
 11. A wound dressing as claimed in claim 1, in which, in theformula: ##EQU3## where R is the percentage proportion by weight ofwater present in the mixture relative to the total water absorbency ofthe copolymer, T is the total water absorbency, x is the percentage byweight of copolymer and Y is the amount of water in the mixing stage, Ris at least 0.7%.
 12. A wound dressing as claimed in claim 11, in whichR is not more than 60%.
 13. A wound dressing as claimed in claim 1,which is contained in a sachet from which the dressing can be extrudedby application of pressure.
 14. A wound dressing as claimed in claim 7in which the distribution of the particles of the copolymer is such thatat least about 90% have a particle size of not more than about 100 μm.15. A gel wound dressing contained in a syringe, the gel wound dressingcomprising a mixture of:(a) a water absorbent polymer of a starch and amonosaturated carboxylic acid or an ester or salt thereof, the copolymerbeing in the form of particles of which at least about 70% by weighthave a size of not more than about 100 μm; and (b) water.
 16. A wounddressing as claimed in claim 15, including a component which reduces thetendency of the dressing to dry out when exposed to the atmosphere. 17.A wound dressing as claimed in claim 15, wherein said componentcomprises a polyol.
 18. A wound dressing as claimed in claim 15, whereinsaid component comprises propane-1,2-diol.
 19. A wound dressing asclaimed in claim 15, wherein said component is present in an amount ofat least 100% based on the weight of the copolymer.
 20. A wound dressingas claimed in claim 15, including an agent which inhibits or at leastreduces the tendency for bacteria to colonize on the dressing.
 21. Awound dressing as claimed in claim 15, wherein the distribution of theparticles of the copolymer is such that at least about 80% have aparticle size of not more than about 100 μm.
 22. A wound dressing asclaimed in claim 15, wherein substantially all of the carboxyl groups inthe copolymer are present as acid groups, or as salt or esterderivatives of said acid groups.
 23. A wound dressing as claimed inclaim 15, wherein said wound dressing comprises a spreadable gelmixture.
 24. A wound dressing as claimed in claim 15, wherein theproportion by weight of copolymer lies in the range from 0.2 to 6%. 25.A wound dressing as claimed in claim 15, wherein, in the formula:##EQU4## where R is the percentage proportion by weight of water presentin the mixture relative to the total water absorbency of the copolymer,T is the total water absorbency, x is the percentage by weight ofcopolymer and Y is the amount of water in the mixing stage, R is atleast 0.7%.
 26. A wound dressing as claimed in claim 15, wherein R isnot more than 60%.